Membrane stabilizing agents, such as lidocaine, prilocaine, mepivacaine and bupivacaine, have been shown to possess local anesthetic effects and are widely used for infiltration anesthesia and for inducing nerve blocks. These compounds have limited use as dermal anesthetics since they have to be given in high concentrations, which increase the risk of toxicity, tissue irritation and tissue damage. Other compounds, such as tetracaine, are better suited for dermal anesthesia since they may better penetrate through the tissues. However, tetracaine and similar drugs are known to cause tissue irritation and ester compounds, like tetracaine are unstable in the human body where practically all tissues contain esterases. Lidocaine also has analgesic activity and is applied dermally as a remedy for neuropathic pain (Lidoderm®).
Objectives of the present invention include providing compounds that are potent membrane stabilizing agents with a prolonged effect as when used to obtain infiltration anesthesia, nerve blocks, topical anesthesia and dermal anesthesia. anesthetics Further objectives of the present invention include providing said potent membrane stabilizing agents with beneficial penetration properties, making said compounds able to penetrate into the ocular tissues, the mucosal tissues, including rectal tissues, and also penetrate into human skin after application on the skin. Thus, the compounds of the invention have short onset time and long duration of anesthesia.
It is also an objective of the present invention to provide a method for analgesia, which is safe, effective, and has a minimum of side effects.
The mechanism of action of membrane stabilizing agents, when used to induce numbness, i.e., for infiltration anesthesia, nerve blocks, topical anesthesia and dermal anesthesia, is to inactivate ion channels in nerves and thereby inhibit neuronal impulse conduction. To do this, the membrane stabilizing compound needs to overcome the local penetration barriers and reach the nerve structure in a concentration that is high enough to achieve the therapeutic objective. The compounds of the present invention have the ability to effectively overcome such tissue penetration barriers.
The mechanism of the analgesic activity of compounds of the present invention, as well as lidocaine, in patients suffering from neuropathic pain, is not known, but is believed to be related to the known effects of these compounds on ion fluxes over biological membranes.
The term topical anesthesia is in this document defined as local anesthesia of mucosal membranes, such as for examples those of the eye, the ear, the mouth, the nose, the rectal area and the urogenital tract. The term dermal anesthesia is in this document defined as local anesthesia of the skin.